Clinical Characteristics and Mortality Among Hypothermic Infants With Herpes Simplex Virus Infection

Hypothermia is considered a risk factor for neonatal herpes simplex virus (HSV) infection. Research evaluating HSV in infants with hypothermia is limited. We sought to describe the prevalence and clinical profile of hypothermic infants with HSV infections who present to pediatric emergency departments (EDs).

We performed a retrospective study of infants (≤90 days of age) with hypothermia (rectal temperature <36.5 °C) presenting to one of 28 tertiary pediatric EDs between January 1, 2013, and December 31, 2022. Using automated data extraction, we described laboratory and clinical characteristics of HSV-positive compared to HSV-negative hypothermic infants.

We analyzed 57,641 infants with hypothermia (median age 23 days [IQR 6-50]; 53.0% male). HSV-positivity from at least one testing site occurred in 126 infants (0.22%; 95% confidence interval [CI] 0.18-0.26%). Of these, 106 (84.1%) had positive cerebrospinal fluid (CSF), 31 (24.6%) had positive blood, and 27 (21.4%) had positive surface HSV testing. The median age of HSV-positive infants was 6 days (IQR 4-12). The median minimum temperature of HSV-positive infants was 35.8 °C (IQR 35.4-36.2 °C). Laboratory studies obtained in hypothermic infants with HSV infection varied, and one HSV-positive infant had concurrent bacteremia. Compared to infants without HSV, infants with HSV were younger (6 vs 23 days; p <0.001), had lower minimum rectal temperature (35.8 vs 36.3 o C; p<0.001), higher rates of intensive care unit admission (57.9% vs 14.3%; p<0.001), higher aspartate aminotransferase (87 vs 47 U/L; p<0.001), and C-reactive protein (0.5 mg/dL vs 0.4 mg/dL; p=0.024). Of infants with HSV, 7/126 died (5.6%, 95% CI 2.3-11.3%), compared to 127/57,515 deaths (0.22%, 95% CI 0.18-0.26%) among infants without HSV (p<0.001).

Neonatal HSV is uncommon in infants with hypothermia in the ED, though mortality in this group is high. Infants with hypothermia and neonatal HSV have distinct clinical characteristics compared to other infants with hypothermia. Further study is needed to delineate risk stratification of hypothermic infants at risk of HSV infection.